School of Pharmaceutical Sciences, Jaipur National University, Jaipur 302 017, Rajasthan, India; Department of Pharmaceutics, STES's Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411 041, Maharashtra, India.
Department of Pharmaceutics, STES's Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411 041, Maharashtra, India.
J Pharm Sci. 2021 Apr;110(4):1761-1778. doi: 10.1016/j.xphs.2021.01.021. Epub 2021 Jan 27.
Delivering therapeutics to the brain using conventional dosage forms is always a challenge, thus the present study was aimed to formulate mucoadhesive nanoemulsion (MNE) of aripiprazole (ARP) for intranasal delivery to transport the drug directly to the brain. Therefore, a TPGS based ARP-MNE was formulated and optimized using the Box-Behnken statistical design. The improved in vitro release profile of the formulation was in agreement to enhanced ex vivo permeation through sheep mucous membranes with a maximum rate of permeation co-efficient (62.87 cm h × 10) and flux (31.43 μg cm.h). The pharmacokinetic profile following single-dose administration showed the maximum concentration of drug in the brain (C) of 15.19 ± 2.51 μg mL and T of 1 h in animals with ARP-MNE as compared to 10.57 ± 1.88 μg mL and 1 h, and 2.52 ± 0.38 μg mL and 3 h upon intranasal and intravenous administration of ARP-NE, respectively. Further, higher values of % drug targeting efficiency (96.9%) and % drug targeting potential (89.73%) of ARP-MNE through intranasal administration were investigated. The studies in Wistar rats showed no existence of extrapyramidal symptoms through the catalepsy test and forelimb retraction results. No ex vivo ciliotoxicity on nasal mucosa reflects the safety of the components and delivery tool. Further, findings on locomotor activity and hind-limb retraction test in ARP-MNE treated animals established its antipsychotic efficacy. Thus, it can be inferred that the developed ARP-MNE could effectively be explored as brain delivery cargo in the effective treatment of schizophrenia without producing any toxic manifestation.
使用传统剂型将治疗药物递送到大脑一直是一个挑战，因此本研究旨在制备阿立哌唑（ARP）的黏膜粘附型纳米乳（MNE）用于鼻腔给药，以便将药物直接递送到大脑。因此，基于 TPGS 的 ARP-MNE 是通过 Box-Behnken 统计设计进行配方和优化的。制剂的改进的体外释放曲线与通过绵羊黏膜的增强的体外渗透一致，具有最大的渗透速率系数（62.87 cm h×10）和通量（31.43μg cm.h）。单次给药后的药代动力学曲线表明，与 ARP-NE 的鼻腔和静脉给药相比，ARPMNE 组动物的脑中药物最大浓度（C）为 15.19±2.51μg mL和 T 为 1 h，而 ARP-NE 组的 C 为 10.57±1.88μg mL和 T 为 1 h，C 为 2.52±0.38μg mL和 T 为 3 h。此外，通过鼻腔给予 ARP-MNE 时，药物靶向效率（96.9%）和药物靶向潜能（89.73%）的更高值得到了研究。在 Wistar 大鼠中的研究表明，通过僵住试验和前肢退缩结果，没有出现锥体外系症状。鼻黏膜无体外细胞毒性反映了成分和传递工具的安全性。此外，在 ARP-MNE 治疗动物的运动活性和后肢退缩试验中的发现建立了其抗精神病功效。因此，可以推断出所开发的 ARP-MNE 可以有效地作为脑递药载体用于治疗精神分裂症，而不会产生任何毒性表现。
